Details of the Drug Combination

General Information of Drug Combination (ID: DCSP3LJ)

• Drug Combination Name: Epirubicin + Nilotinib
• Indication: Amelanotic melanoma; Status: Investigative [1]
• Component Drugs:
  Epirubicin (DMPDW6T): Small molecular drug
  Nilotinib (DM7HXWT): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: M14
  Zero Interaction Potency (ZIP) Score: 3.35
  Bliss Independence Score: 3.71
  Loewe Additivity Score: 2.27
  LHighest Single Agent (HSA) Score: 0.25

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Epirubicin

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Approved	[2]

Epirubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[4]

Epirubicin Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[5]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[6]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[6]

Epirubicin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[7]

Epirubicin Interacts with 30 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-binding cassette sub-family C member 2 (ABCC2)	OTJSIGV5	MRP2_HUMAN	Increases Expression	[8]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Increases Expression	[8]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[8]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Decreases Response To Substance	[9]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Increases Expression	[10]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Expression	[11]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[12]
Interleukin-6 receptor subunit alpha (IL6R)	OTCQL07Z	IL6RA_HUMAN	Increases Expression	[13]
Retinoic acid receptor alpha (RARA)	OT192V9V	RARA_HUMAN	Affects Mutagenesis	[14]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Increases Expression	[8]
Ribosomal protein S6 kinase beta-1 (RPS6KB1)	OTAELNGX	KS6B1_HUMAN	Increases Phosphorylation	[15]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Increases Phosphorylation	[15]
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Increases Phosphorylation	[15]
Protein PML (PML)	OT6SM2GD	PML_HUMAN	Affects Mutagenesis	[14]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Expression	[16]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Expression	[11]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[11]
Eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1)	OTHBQVD5	4EBP1_HUMAN	Increases Phosphorylation	[15]
FK506-binding protein-like (FKBPL)	OTR9ND6K	FKBPL_HUMAN	Increases Expression	[16]
Tumor necrosis factor receptor superfamily member 1A (TNFRSF1A)	OT2D9DOV	TNR1A_HUMAN	Increases ADR	[17]
MARVEL domain-containing protein 1 (MARVELD1)	OT5CPOJE	MALD1_HUMAN	Increases Response To Substance	[18]
Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP)	OT9AGAIJ	LHPP_HUMAN	Increases ADR	[17]
Alpha-protein kinase 1 (ALPK1)	OTBW6SGD	ALPK1_HUMAN	Increases ADR	[19]
Baculoviral IAP repeat-containing protein 6 (BIRC6)	OTCQJAB0	BIRC6_HUMAN	Decreases Response To Substance	[20]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Response To Substance	[21]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Affects Response To Substance	[22]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Response To Substance	[23]
Pleckstrin homology-like domain family A member 2 (PHLDA2)	OTMV9DPP	PHLA2_HUMAN	Increases Response To Substance	[24]
Little elongation complex subunit 1 (ICE1)	OTOXTBUH	ICE1_HUMAN	Increases ADR	[17]
Microcephalin (MCPH1)	OTYT3TT5	MCPH1_HUMAN	Increases ADR	[19]

Indication(s) of Nilotinib

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[3]

Nilotinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Fusion protein Bcr-Abl (Bcr-Abl)	TTS7G69	BCR_HUMAN-ABL1_HUMAN	Modulator	[28]

Nilotinib Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[29]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[30]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[29]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[31]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[31]

Nilotinib Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[32]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[33]

Nilotinib Interacts with 35 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2)	OTW8V2V1	ABCG2_HUMAN	Affects Response To Substance	[34]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Affects Response To Substance	[35]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[36]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Increases Activity	[36]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[36]
Acetyl-CoA carboxylase 1 (ACACA)	OT5CQPZY	ACACA_HUMAN	Increases Phosphorylation	[36]
Retinal dehydrogenase 2 (ALDH1A2)	OTJB560Z	AL1A2_HUMAN	Decreases Expression	[26]
Tyrosine-protein kinase ABL1 (ABL1)	OT09YVXH	ABL1_HUMAN	Decreases Phosphorylation	[27]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Increases Expression	[27]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Secretion	[37]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[27]
Homeobox protein Hox-B7 (HOXB7)	OTC7WYU8	HXB7_HUMAN	Increases Expression	[26]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Increases Cleavage	[38]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[38]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[27]
Breakpoint cluster region protein (BCR)	OTCN76C1	BCR_HUMAN	Decreases Phosphorylation	[39]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Increases Expression	[27]
Homeobox protein Hox-B9 (HOXB9)	OTMVHQOU	HXB9_HUMAN	Increases Expression	[26]
Cyclic AMP-dependent transcription factor ATF-6 alpha (ATF6)	OTAFHAVI	ATF6A_HUMAN	Decreases Expression	[27]
Histidine decarboxylase (HDC)	OT4WA5YQ	DCHS_HUMAN	Decreases Expression	[40]
Paired box protein Pax-3 (PAX3)	OTN5PJZV	PAX3_HUMAN	Decreases Expression	[26]
Alanine aminotransferase 1 (GPT)	OTOXOA0Q	ALAT1_HUMAN	Increases Secretion	[41]
Paired box protein Pax-6 (PAX6)	OTOC9876	PAX6_HUMAN	Increases Expression	[26]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[27]
Crk-like protein (CRKL)	OTOYSD1R	CRKL_HUMAN	Decreases Phosphorylation	[27]
Glutamate--cysteine ligase regulatory subunit (GCLM)	OT6CP234	GSH0_HUMAN	Increases Expression	[27]
Homeobox protein MOX-1 (MEOX1)	OTJEMT2D	MEOX1_HUMAN	Decreases Expression	[26]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Cleavage	[38]
Mesoderm posterior protein 2 (MESP2)	OT7H4LYA	MESP2_HUMAN	Decreases Expression	[26]
Transcription factor 15 (TCF15)	OTA6UCWC	TCF15_HUMAN	Decreases Expression	[26]
Oligodendrocyte transcription factor 3 (OLIG3)	OTU8XLAF	OLIG3_HUMAN	Increases Expression	[26]
ER degradation-enhancing alpha-mannosidase-like protein 1 (EDEM1)	OTWHN69S	EDEM1_HUMAN	Increases Expression	[27]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Decreases Expression	[26]
Forkhead box protein C2 (FOXC2)	OT83P1E0	FOXC2_HUMAN	Decreases Expression	[26]
Neurogenin-2 (NEUROG2)	OTAEMIGT	NGN2_HUMAN	Increases Expression	[26]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DCXR942	MOLT-4	Investigative	[42]
Childhood T acute lymphoblastic leukemia	DCQ9I1C	CCRF-CEM	Investigative	[42]
Clear cell renal cell carcinoma	DCRGVK6	TK-10	Investigative	[42]
Clear cell renal cell carcinoma	DCSZOHW	CAKI-1	Investigative	[42]
Plasma cell myeloma	DC06YTC	RPMI-8226	Investigative	[42]
Renal cell carcinoma	DCVD9SH	SN12C	Investigative	[42]
Breast adenocarcinoma	DC9VP31	MDA-MB-468	Investigative	[43]
Invasive ductal carcinoma	DCQPFDR	BT-549	Investigative	[43]
Invasive ductal carcinoma	DCB1CPE	HS 578T	Investigative	[43]
Adenocarcinoma	DCPERFJ	NCIH23	Investigative	[1]
Amelanotic melanoma	DCKSHZ3	MDA-MB-435	Investigative	[1]
Cutaneous melanoma	DC5HPSB	SK-MEL-28	Investigative	[1]
Large cell lung carcinoma	DCM3X3V	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DCXS4LX	EKVX	Investigative	[1]
Lung adenocarcinoma	DC5X111	NCI-H522	Investigative	[1]
Melanoma	DC6PCLO	UACC-257	Investigative	[1]
Melanoma	DCQNE9P	SK-MEL-2	Investigative	[1]
Minimally invasive lung adenocarcinoma	DC6IPWP	NCI-H322M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCZF40V	IGROV1	Investigative	[1]
Non-small cell lung carcinoma	DCERP20	HOP-92	Investigative	[1]
Pleural epithelioid mesothelioma	DCDG5HP	NCI-H226	Investigative	[1]
Prostate carcinoma	DCXIFZT	PC-3	Investigative	[1]

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